IFN alpha and gamma are produced by immune cells in the body and regulate immune functions such as antibody production, expression of cell-surface antigens and T cell maturation and differentiation. IFN gamma is also the best known and characterized macrophage activating factor. In recent years, IFN gamma has been shown to exert a suppressive effect on infections caused by a wide range of nonviral pathogens including rickettsiae, chlamydiae, fungi, bacteria and protozoa. Furthermore, in concert with other cytokines, IFN gamma has been shown to be involved in the regulation of acute inflammatory responses to bacterial lipopolysaccharides.
The bacterium Actinobacillus (Haemophilus) pleuropneumoniae is the cause of an often fatal respiratory disease in swine known as porcine Haemophilus pneumonia (PHP). The acute form of the disease is manifested by the sudden onset of clinical manifestations and high mortality. Early symptoms of the acute form of the disease include elevated temperature, respiratory distress, cyanosis, vomiting, lethargy and depression. However, sudden death is often the only clinical manifestation in some animals. PHP is not always fatal; some swine become infected and remain asymptomatic carriers. Significant economic losses also arise from the development of chronic lesions with subsequent reduction of productive performance in the survivors.
The pathogenesis of PHP has not been completely elucidated. Nevertheless, the pathology caused by A. pleuropneumoniae in the peracute and acute forms of the disease has been compared to that of endotoxic shock. The lesions consist of alveolar and interlobular edema, congestion, endothelial damage and hemorrhage, and intravascular fibrinous thrombosis. The end result is commonly acute circulatory collapse. It has been shown that intravenous (IV) injection of sterile PHP pneumonia lung suspension in pigs induces bilateral renal cortical necrosis, similar to that seen in a generalized Schwartzman reaction. The Schwartzman reaction can be induced with most gram-negative bacteria and, in some instances, this reaction becomes an important component of the disease pathogenesis.
Studies on the regulation of LPS-induced Schwartzman reaction have shown that antibodies against IFN gamma as well as parenteral administration of all IFN types suppress the local Schwartzman reaction. These results have been used to postulate that, within the inflammatory focus, IFN gamma acts as a pro-inflammatory cytokine, while in the circulation they exhibit anti-inflammatory properties. These anti-inflammatory properties of systemic IFN's have been suggested to be mediated indirectly through centrally regulated endocrine or neuroendocrine mechanisms. IFN alpha has also been suggested to play a role in the regulation of acute inflammatory responses.
The use of anti-IFN gamma has been proposed to aid in the control of clinical manifestations resembling a Schwartzman reaction such as acute inflammatory reactions associated with acute vascular thrombosis and certain chronic disorders associated with uncontrolled macrophage activation. All attempts to prevent and control PHP have met with limited success.
The following references are of general interest regarding IFN gamma and PHP:
Haemophilus pleuropneumoniae of Pigs, VIDO Views, Fact Sheet No. 10, April 1985.
Sebunya, T.N.K. and Saunders, J.R. (1983) Haemophilus pleuropneumoniae Infection in Swine: A Review. J.A.V.M.A. 182:1331-1337.
Billiau, A. (1980) Gamma Interferon: The Match that Lights the Fire. Immunol. Today 9:37-40.
Heremans, H. et al. (1987) Regulation by Interferons of the Local Inflammatory Response to Bacterial Lipopolysaccharide. J. Immunol. 130:4175-4179.
Kiderlen, A.F. et al. (1984) Protection of Mice Against Intracellular Bacterium Listeria Monocytogenes by Recombinant Immune Interferon. Eur. J. Immunol. 14:964-967.
Buchmeier, N. et al. (1985) Requirement of Endogenous Interferon- Production for Resolution of Listeria Monocytogenes Infection. Proc. Natl. Acad. Sci. USA 82:7404-7408.
Bhardwaj, N. et al. (1986) Gamma Interferon- Activated Human Monocytes Inhibit the Intracellular Multiplication of Legionella Pneumophilia. J. Immunol. 137:2662-2669.
Edwards III, C.K. et al. (1986) Chronic Infection Due to Mycobacterium Intracellulare in Mice. Association with Macrophage Release of Prostaglandin E2 and Reversal by Injection of Indomethacin, Muramyl Dipeptide or Interferon. J. Immunol. 136:1820-1827.
Charley, B. et al. (1988) Antiviral and Antigenic Properties of Recombinant Porcine Interferon Gamma. Vet. Immunol. & Immunopath. 19:95-103.